Cell therapy clinical trials 2009 – part II

by Alexey Bersenev on April 28, 2009 · 1 comment

in clinical trials and cases

Fresh digest of published clinical trials and cases, which captured my attention in last 2 months. The feature of today’s review – absence of trials done in USA.


C-peptide levels and insulin independence following autologous nonmyeloablative hematopoietic stem cell transplantation in newly diagnosed type 1 diabetes mellitus (Brazil)

After a mean follow-up of 29.8 months following autologous nonmyeloablative HSCT in patients with newly diagnosed type 1 DM, C-peptide levels increased significantly and the majority of patients achieved insulin independence with good glycemic control.

leukemia – donor cells control

Infusion of suicide-gene-engineered donor lymphocytes after family haploidentical haemopoietic stem-cell transplantation for leukaemia (the TK007 trial): a non-randomised phase I-II study (Europe – International)

In a phase I—II, multicentre, non-randomised trial of haploidentical stem-cell transplantation, we infused donor lymphocytes expressing herpes-simplex thymidine kinase suicide gene (TK-cells) after transplantation
28 patients received TK-cells starting 28 days after transplantation; 22 patients obtained immune reconstitution at median 75 days (range 34—127) from transplantation and 23 days (13—42) from infusion. Ten patients developed acute GVHD (grade I—IV) and one developed chronic GVHD, which were controlled by induction of the suicide gene.

read more

leukemia – MSC infusion

Infusion of mesenchymal stromal cells can aid hematopoietic recovery following allogeneic hematopoietic stem cell myeloablative transplant: a pilot study (Belgium)

In this pilot study, we evaluated the safety and efficiency of donor expanded MSC infusion after allogeneic hematopoietic stem cell transplantation (HSCT) in six patients with poor hematopoietic recovery.
Two patients displayed rapid hematopoietic recovery (days 12 and 21), and four patients showed no response. The two patients who showed hematopoietic recovery were in first complete remission compared to the other heavily pretreated patients. There were no toxic side effects linked to MSC infusion.
Our data suggest that patients with a less damaged stroma could benefit from this approach.

gene therapy

VEGF gene therapy fails to improve perfusion of ischemic myocardium in patients with advanced coronary disease: results of the NORTHERN trial (Canada)

A total of 93 patients with refractory Canadian Cardiovascular Society (CCS) class 3 or 4 anginal symptoms were randomized to receive 2,000 microg of VEGF plasmid DNA or placebo (buffered saline) delivered via the endocardial route using an electroanatomical NOGA guidance catheter.
Despite the intramyocardial administration of a high “dose” of plasmid DNA using a percutaneous guidance catheter system, there was no benefit of VEGF gene therapy at 3 or 6 months for any of the end points studied.

read one more gene therapy FAIL

neurology – spinal cord injury

Stem cells in the treatment of chronic spinal cord injury: evaluation of somatosensitive evoked potentials in 39 patients (Brazil)

Thirty-nine consecutive patients with diagnosed complete cervical and thoracic SCI for at least 2 years and with no cortical response in the SSEP study of the lower limbs were included in the trial. The trial patients underwent peripheral blood stem cell mobilization and collection.
Twenty-six (66.7%) patients showed recovery of somatosensory evoked response to peripheral stimuli after 2.5 years of follow-up.

cancer – immunotherapy

Combination therapy of in vitro-expanded natural killer T cells and α-galactosylceramide-pulsed antigen-presenting cells in patients with recurrent head and neck carcinoma (Japan)

The aim of this clinical trial was to investigate the feasibility of intra-arterial infusion of in vitro-expanded Vα24 natural killer T (NKT) cells combined with submucosal injection of α-galactosylceramide (KRN7000; αGalCer)-pulsed antigen-presenting cells (APC). A phase I clinical study was carried out in patients with head and neck squamous cell carcinoma (HNSCC). Patients with locally recurrent HNSCC refractory to standard therapy were eligible.
Regarding the clinical responses, three cases exhibited a partial but significant response, four were classified as stable disease, and one patient continued to develop progressive disease. The use of the intra-arterial infusion of activated Vα24 NKT cells and the submucosal injection of αGalCer-pulsed APC has been shown to induce significant antitumor immunity and had beneficial clinical effects in the management of advanced HNSCC. The use of such therapeutic modalities may be helpful in the management of tumors and therefore needs to be explored in further detail.

tissue engineering

Effectiveness of haemodialysis access with an autologous tissue-engineered vascular graft: a multicentre cohort study (International)

Application of a tissue-engineered vascular graft for small-diameter vascular reconstruction has been a long awaited and much anticipated advance for vascular surgery. We report results after a minimum of 6 months of follow-up for the first ten patients implanted with a completely biological and autologous tissue-engineered vascular graft.
Overall, primary patency was maintained in seven (78%) of the remaining nine patients 1 month after implantation and five (60%) of the remaining eight patients 6 months after implantation.

cases reports:
Allogeneic mesenchymal stem cells transplantation in treatment of multiple sclerosis
Non-expanded adipose stromal vascular fraction cell therapy for multiple sclerosis
Histological findings on fetal striatal grafts in a Huntington’s disease patient early after transplantation


also read:
Cell Therapy Clinical Trials in 2008 – part I
Cell Therapy Clinical Trials in 2008 – part II
Cell therapy clinical trials in 2009 – part I
more clinical trials

picture credit: “Display Direct” via Flickr

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{ 1 comment… read it below or add one }

David DiGiusto May 22, 2009 at 4:15 pm

Completed late last year at City of Hope Conprehensive Cancer Center…

Autologous peripheral blood progenitor cell (PBPC) transplantation for HIV-related lymphoma allows the assessment of vector mediated gene transfer. CD34+ PBPC were isolated from G-CSF-mobilized apheresis products and transduced with a self-inactivating lentiviral vector encoding 3 RNA-based anti-HIV moieties (Tat/Rev shRNA, TAR decoy and CCR5 ribozyme) and then infused. One-day following this, an aliquot of unmanipulated PBPC product was infused. Five patients were studied and 4 received both PBPC infusions. Our in vitro analysis showed that multiple lineages of gene-marked blood cells had initial levels of marking as high as 22%, but then declined rapidly to approximately 1% in 3-4 week cultures. No differences were observed in the frequency or lineage distribution of blood cells derived from transduced and non-transduced populations. Expression of all three RNA species could be demonstrated in mature blood cells derived from in vitro culture of these cells. Patients transplanted with gene modified and unmodified CD34+ cells engrafted with an (ANC >500) by 11 days. No serious adverse events were observed. Subjects have been followed for up to 12 months and gene marking, including siRNA expression, was seen at multiple time points in the peripheral blood of all patients. The percent marking in peripheral blood (0.02-0.2%) was consistent with the input % transduced cells infused (0.11-0.15%) and continues to be followed. Quantifiable expression of shRNA above background in the peripheral blood of all patients has been observed. This is the first demonstration of sustained siRNA expression in human blood cells derived from ex vivo gene- modified progenitor cells. Taken together, these results support the development of an RNA-based cell therapy platform for HIV.


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